-to minimize graft rejection

-minimize rejection without suppressing entire immune response

self-tissue grafted to another self area (skin grafts, blood vessels)

tissue transferred between different species (baboon heart into a human)

-animal of different species 

• cells
• tissues
• organs

• Kidney
• pancreas: common for type 1 diabetes
• heart
• lung
• bone marrow
• cornea: really successful 

• CD4+ & CD8+ T cells recognize alloantigens expressed on foreign graft cells
• The T cells proliferate in response
• may recognize the donor MHC molecules directly (direct presentation).
• May recognize peptides from donor MHC's presented in the recipient's own APC MHC molecules (indirect presentation)
• Memory T cells generated

• variety of mechanisms participate in effector stage of graft rejection
• generally involves heavy infiltration of recipient cells into graft tissue (similar to a DTH reaction)
• can rarely involve production of antibody against donor HLA molecules or endothelial Ag

• develops months or years after acute rejection reactions have subsided
• mechanisms include humoral & cell-mediated recipient responses
• Anti-rejection drugs help, but are not perfect
• 1 year kidney grafts survival rates were 97% in the United States in 2008
• 10-year survival rates were only 60%
• Work continues to make allograft transplants last longer or avoid rejection altogether

1. stage 1 (mild): a skin rash over less than 25% of the body
2. stage 2 (moderate): a skin rash over a more than 25% of the body accompained by mild liver or stomach and intestinal disorders
3. stage 3 (severe): redness of the skin, similar to a severe sunburn, and moderate liver, stomach, and intestinal problems.
4. stage 4 (life-threatening): blistering, peeling skin, and severe liver, stomach, and intestinal problems. 

• It's a type of generalized immunosuppressive therapy. 
• it's a mitotic inhibitor that diminshes B & T cell proliferation
• can dramatically increase survival rates of allografts

• It's a type of generalized immunosuppressive therapy
• cyclophosphamide inserts into the DNA helix, disrupting it

• most common; easier surgically than some 
• the door survives
• diseases like diabetes & various type of nephritis can be elevated by kidney transplantation.
• survival rate after one year transplantation is >90%
• 25,000 candidates are waiting for kidney transplantation
• transplat recipients are sensitized to further transplants

• recipient is immunosuppressed before graft
• graft vs. host disease is common (50-70%)
• TNF-Beta is a major player

-immunosuppression: current treatment along with some (bottom)

-donor T cell depletion (partial; some activity needed against host T cells)

   -in order to not make memory

   -so when you get donor, no memory partial,          don't make or attack your own cells. 

• first heart transplant in South African by Dr. Christian Barnard in 1964
• one year survival rate is >80%
• HLA matching is desirable but not often possible, because of the limited supply of heart and the surgery and the urgency of the procedure
• surgery is quite successful
• MHC matching is often not feasible;
• massive immunosuppression
• tranplants seem to be prone to coronary disease

• sometimes go with heart
• transplants are still rare
• first attempt in 1963 by Hardy and Co-workers
• first successful transplantation by Toronto group in 1983.
• in conjunction with heart transplantation, to treat diseases such as cystic and emphysema or acute damage to lungs
• first year survival rate is about 60%

• parts have been grafted successfully
• resistant to antibody mediated toxicity
• but not GVHD
• relatively difficult surgery
• it treated congenital defects & damage from viral (hepatitis) or chemical agents (Chronic alcoholism)
• liver one year survival exceeds 75% and fiver year is 70%

• functional parts (islet cells)
• still rare
• offers a cure for diabetes mellitus
• graft survival is 72% at one year
• further improved if a kidney is transplanted simultaneously
• overall goal: to prevent the typical diabetic secondary complications

• usually autologous
• burn victims: tissue bank donors have been used.
• more than 25% of their body
• they live in isolation
• you lost the first initial barrier
• and if you get bacteria
• immunosuppression is a problem because a burn patient is vulnerable to infection
• cause they try to put skin on you

• "Protected" site
• local immunosuppression
• uterine epithelium and trophoblast* secrete
• cytokines that suppresses TH1 (the most)
• placenta secretes a substance that depletes tryptophan: T cell starvation?
• This is what they think what happens, but they're not sure.
• tolerance of paternal MHC antigens?
• *outer layer of placenta; does not express MHC
• class I and class II antigens

• baby Fae ---> Baboon heart in 1984
• survived 35 days
• promising but controversial
• better to meet the demand?
• nonhuman primates-have not been particularly successful, and not that common anyway.
• transgenic pigs:
• organs are similar size and structure
• are being engineered to have human antigens and/or immunosuppressive capacities
• can be bred in large numbers and under controlled conditions

• transplantation of Bone
• April 2014 First Full Transplantation
• Functioning liver
• Both hepatocytes and epithelial cells
• Full tissue?